De Novo Metabolic Syndrome 1 Year after Liver Transplantation and Its Association with Mid- and Long-Term Morbidity and Mortality in Liver Recipients.

Background: Metabolic syndrome (MS) constitutes an important source of cardiovascular- and cancer-related morbidity and mortality in the general population. Limited information is available on whether these findings can be directly extrapolated to liver recipients. This study aimed to investigate the impact of post-transplant MS present 1 year after liver transplantation on survival rates, risk of major cardiovascular events (CVEs), and de novo malignancies. Methods: Adult deceased-liver-donor recipients who underwent transplantation in our centre between 2010 and 2019 and reached at least 1 year of post-transplantation follow-up were eligible. Results: Of 259 enrolled patients, 20% developed post-transplant MS 1 year after the procedure. The presence of post-transplant MS at 1 year did not affect all-cause mortality (p = 0.144) and risk of de novo malignancies (p = 0.198) in liver recipients. However, it was associated with an overall and time-dependent increase in the risk of major CVEs (p < 0.001). MASH aetiology of liver disease, pre-existing major CVEs, and development of de novo malignancy were independent predictors of all-cause mortality in liver recipients. Conclusions: New onset MS exerts a wide-ranging effect on the post-transplant prognosis of liver recipients. Obtaining optimal control over all modifiable metabolic risk factors is central to improving long-term outcomes in this population.

DRESS Syndrome: Renal Involvement in Two Cases - A Comprehensive Analysis and Literature Review of Improved Diagnosis and Treatment.

BACKGROUND Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare hypersensitivity reaction involving the skin and various visceral organs; the kidneys are the second most affected organ. Many drugs are reported to be associated with DRESS, particularly antiepileptic agents and allopurinol. Certain human leukocyte antigen (HLA) haplotypes, in combination with a particular drug, can further contribute to an increased risk of DRESS. Symptoms often develop 2 to 8 weeks after drug initiation. If diagnosis is delayed, DRESS can be a life-threatening condition. CASE REPORT We present cases of 2 patients. The first patient was an 86-year-old Polish woman who developed acute kidney injury and skin lesions with accompanying leucocytosis and eosinophilia during long-term antibiotic therapy with piperacillin/tazobactam and ciprofloxacin. The second patient was a 37-year-old Asian woman with predialysis chronic renal disease stage V in the course of IgA nephropathy. Two weeks after starting allopurinol in a standard dose, she presented with maculopapular rash, facial edema, fever, liver injury, and eosinophilia. Renal function started to deteriorate, but she did not require dialysis. In both cases, the discontinuation of the above-mentioned drugs and the introduction of steroid therapy and intravenous immunoglobulins allowed for clinical improvement and recovery. In the second case, the extended 4-locus HLA typing was performed retrospectively, and allele HLA-B*5801 was found. CONCLUSIONS Due to the rare occurrence and heterogeneous manifestation of DRESS, its diagnosis can pose many difficulties. In-depth analysis of symptoms, medicines taken, and laboratory findings enable the implementation of appropriate treatment and recovery.

The Importance of 1-Year Protocol Biopsy in the Long-Term Prognosis of Kidney Transplants-5-Years Follow-Up.

BACKGROUND: Protocol biopsies are performed to detect subclinical pathologies that may lead to future graft dysfunction. However, they are not routinely performed interventions in every transplant center. There is no established regimen for performing them. PURPOSE: The study aimed to evaluate if protocol biopsies can improve long-term patient outcomes after detecting early disorders and modifying treatment. MATERIAL AND METHODS: Our observational study included 61 patients who underwent protocol biopsy 12 months after the transplantation. Based on the biopsy results, patients with abnormal histologic material (n = 37) were divided into 3 study groups as follows: patients with mild inflammatory lesions (n = 21), patients with interstitial fibrosis and tubular atrophy (IFTA) grade II to III (n = 12), and patients with BK virus nephropathy (n = 4). The control group (n = 24) included kidney recipients with IFTA 0 to I grade. Outcomes after 5-year follow-up were evaluated. RESULTS: Five years after the biopsy, patients in the control group had stable graft function (5-year change in serum creatinine was -0.09 mg/dL). An increase in serum creatinine levels was observed in patients with IFTA II to III compared with the control group (0.14 mg/dL, P = .04). Immunosuppressive treatment was modified in the group with mild inflammatory changes and in the BKV group after the biopsy result. In the group with mild inflammatory lesions, renal function was stable (change of serum creatinine was -0.01 mg/dL, P = .51). In the BKV nephropathy group, there was a significant reduction in serum creatine levels (-0.48 mg/dL, P = .016). The analysis showed no diagnostic value for serum creatinine concentration (95% CI 0.49-0.78, P = .08). CONCLUSIONS: Protocol biopsies are useful for detecting early pathologies and preventing allograft failure. They greatly benefit patients with detectable pathology that can be treated or in whom therapy modification is possible.

Potential utility of urinary chemokine CCL2 to creatinine ratio in prognosis of 5-year graft failure and mortality post 1-year protocol biopsy in kidney transplant recipients.

BACKGROUND: Chemokines (chemotactic cytokines) are small proteins which are engaged in many pathophysiological processes, including inflammation and homeostasis. In recent years, application of chemokines in transplant medicine was intensively studied. The aim of this study was to determine the utility of urinary chemokines CCL2 (C-C motif ligand 2) and CXCL10 (C-X-C motif chemokine ligand 10) in prognosis of 5-year graft failure and mortality post 1-year protocol biopsy in renal transplant recipients. METHODS: Forty patients who had a protocol biopsy 1 year after renal transplantation were included. Concentrations of CCL2 and CXCL10 in urine with reference to urine creatinine were measured. All patients were under the supervision of one transplant center. Long-term outcomes within 5 years after 1-year posttransplant biopsy were analyzed. RESULTS: Urinary CCL2:Cr at the time of biopsy was significantly increased in patients who died or had graft failure. CCL2:Cr was proven to be a significant predictor of 5-year graft failure and mortality (odds ratio [OR]: 1.09, 95% confidence interval [CI]: 1.02-1.19, p = .02; OR: 1.08, 95% CI: 1.02-1.16, p = .04; respectively). CONCLUSION: Chemokines are easily detected by current methods. In the era of personalized medicine, urinary CCL2:Cr can be considered as a factor providing complementary information regarding risk of graft failure or increased mortality.

Impact of Resolved Preformed, Persistent Preformed, and De Novo Anti-HLA Donor-Specific Antibodies in Kidney Transplant Recipients on Long-Term Renal Graft Outcomes.

The post-transplant evolution of antihuman leukocyte antigen donor-specific antibodies (anti-HLA DSAs) includes three clinical patterns: resolved preformed DSAs, persistent preformed DSAs, and de novo DSAs. The aim of this retrospective study was to analyze the impact of resolved preformed, persistent preformed, and de novo anti-HLA-A, -B, and -DR DSAs in kidney transplant recipients on long-term renal allograft outcomes. This is a post hoc analysis of the study conducted in our transplant center. One hundred eight kidney transplant recipients were included in the study. Patients were followed for a minimum of 24 months after allograft biopsy, which was performed 3 to 24 months after kidney transplantation. The identification of persistent preformed DSAs at the time of biopsy was the most significant predictor of the combined endpoint of the study (>30% decline in estimated glomerular filtration rate or death-censored graft loss; HR = 5.96, 95% CI 2.041-17.431, p = 0.0011), followed by the occurrence of de novo DSAs (HR = 4.48, 95% CI 1.483-13.520, p = 0.0079). No increased risk was observed in patients with resolved preformed DSAs (HR = 1.10, 95% CI 0.139-8.676, p = 0.9305). Patients with resolved preformed DSAs have similar graft prognoses as patients without DSAs, therefore, the persistence of preformed DSAs and development of de novo DSAs are associated with inferior long-term allograft outcomes.

Nephro-oncology: clinical and biochemical aspects of kidney disease and cancer.

Onco-nephrology is a new field of medicine which combines many aspects of kidney injury in cancer patients and cancers in patients with kidney disease. This connection takes many forms and includes drug-induced nephrotoxicity, electrolyte disorders, numerous paraneoplastic syndromes and an increased rate cancers in dialysis and transplanted patients. The appropriate laboratory assessment of the kidney function allows to optimize chemotherapy and thus minimizes the risk of complications. This article focuses on acute kidney injury (AKI), chronic kidney disease (CKD), various electrolyte and acid-base disorders, the most common cancers after kidney transplantation and the kidney disorders associated with HSCT (hematopoietic stem cell transplantation). The possibility of the application of novel cancer therapy, such as cancer immunotherapy and proton therapy in transplant recipients was also discussed.

Are We on the Right Track for HCV Micro-Elimination? HCV Management Practices in Dialysis Centers in Poland-A National Cross-Sectional Survey.

Chronic hepatitis C (CHC) is prevalent in the hemodialysis-dependent population. Currently, all patients with CHC should be considered for treatment; however, many hemodialysis-dependent patients are still left untreated. Following HCV cure, accurate surveillance is mandatory to reduce liver-related mortality and prevent reinfection. We aimed to establish HCV management practices and barriers to HCV elimination in dialysis centers in Poland. Polish dialysis centers were surveyed via email. The HCV management strategies were investigated. Representatives of 112 dialysis centers responded, representing 43.1% of all dialysis centers in Poland and 43.4% of hemodialysis-dependent patients' volume. Most respondents were Heads of hemodialysis centers and board-certified nephrologists. The study demonstrated that in the vast majority of hemodialysis centers (91.6%), subjects are considered for antiviral treatment (AVT); however, many obstacles preventing patients from being prescribed AVT were identified; patients' reluctance to undergo AVT was most reported (60%). The majority of dialysis units neither evaluate patients with CHC for liver fibrosis (60.4%) nor screen them for hepatocellular carcinoma (53.5%). In conclusion, the presented study demonstrates that HCV management practices across Polish dialysis centers vary substantially. There is a need to optimize and streamline the HCV management infrastructure in the hemodialysis population in Poland.

Difficulties in the Diagnosis of Fibrinogen Aα-Chain Amyloidosis-Literature Review and Case Report of a Patient After Kidney Transplantation.

BACKGROUND: Amyloidosis is a very heterogeneous disease. Correct diagnosis is extremely important because of the various treatment options for different types of amyloidosis. This study presents a case report and literature review of the misdiagnosis of fibrinogen Aα-chain amyloidosis (AFib amyloidosis). CASE PRESENTATION: We report a 65-year-old man diagnosed with proteinuria in 2009. The kidney biopsy revealed the presence of Congo red-stained amyloid deposits. During differential diagnosis, amyloid deposits were discovered in adipose tissue and gingiva. Bone marrow trephine biopsy showed a predominance of lambda chains presenting plasmocytes. Based on performed medical examination, light chain amyloidosis was identified. Therefore, the patient received high-dose melphalan and underwent successful autologous peripheral blood stem cell transplantation. However, proteinuria, worsening of the kidneys' function, and incorrect levels of free light chains were still observed. In 2019, due to continuous treatment failure, a previously acquired kidney biopsy was examined by mass spectrometry, and numerous fibrinogen deposits were identified. Recommended DNA analysis revealed that the patient had AFib amyloidosis. Therefore, chemotherapy treatment was abandoned, and successful kidney transplantation was performed. CONCLUSION: Today, it is essential for medical practitioners to remember the possibility of rare and hereditary types of amyloidosis. There are multiple cases where a diagnosis was wrong or delayed because of the atypical course of the disease, the coexistence of another disease, and the rarity of AFib amyloidosis, and all of these reasons may result in the wrong treatment that will delay the right therapy. However, with the new, more precise diagnostics methods, such situations will become rare.

Association of Circulating Anti-HLA Donor-Specific Antibodies and Their Characteristics, including C1q-Binding Capacity, in Kidney Transplant Recipients with Long-Term Renal Graft Outcomes.

Post-transplant antihuman leukocyte antigen donor-specific antibodies (anti-HLA DSAs) monitoring in kidney transplant recipients remains unclear and is currently under investigation. The pathogenicity of anti-HLA DSAs is determined by antibody classes, specificity, mean fluorescent intensity (MFI), C1q-binding capacity, and IgG subclasses. The aim of this study was to investigate the association of circulating DSAs and their characteristics with renal allograft long-term outcomes. The study included 108 consecutive patients from our transplant center who underwent kidney allograft biopsy between November 2018 and November 2020, 3 to 24 months after kidney transplantation. At the time of biopsy, patients' sera were collected for analysis of anti-HLA DSAs. Patients were followed for a median time of 39.0 months (Q1-Q3, 29.8-45.0). Detection of anti-HLA DSAs at the time of biopsy (HR = 5.133, 95% CI 2.150-12.253, p = 0.0002) and their C1q-binding capacity (HR = 14.639, 95% CI 5.320-40.283, p ≤ 0.0001) were independent predictors of the composite of sustained 30% reduction from estimated glomerular filtration rate or death-censored graft failure. Identification of anti-HLA DSAs and their C1q-binding capacity could be useful in identifying kidney transplant recipients at risk for inferior renal allograft function and graft failure. Analysis of C1q is noninvasive, accessible, and should be considered in clinical practice in post-transplant monitoring.

Antiphospholipid Syndrome in Renal Allograft Recipients-A Long-Term Multicenter Analysis.

Antiphospholipid syndrome (APS) is a devastating autoimmune disease and in renal transplant recipients may result in allograft thrombosis or in extra-renal manifestation, mostly venous thromboembolism. There are many non- and immune risk factors affecting renal allograft in recipients with APS. However, renal allograft outcome in recipients with APS without APS nephropathy remains unknown. Aim: The aim of the study was to assess renal allograft function and survival in recipients with APS. Methods: Retrospective, multicenter study included 19 adult renal recipients with definite APS (primary or lupus-related) from three Polish transplant centers. Renal allograft function was assessed using serum creatinine concentration (SCr1) at 3rd month post-transplant and at the end of the observation (SCr2) and glomerular filtration rate (GFR) was estimated based on modification of diet in renal disease (MDRD) formula. General linear model was used to assess 12 month GFR change over time. Kaplan-Meier curves and restricted mean survival time were used for allograft survival. Matched control group consisted of 21 stable renal recipients without history of thrombosis and without anticoagulation/antiplatelet treatment. Results: The study group differs in induction therapy (p = 0.019), high-urgency procedure (p = 0.04), proteinuria (p = 0.0058), primary disease (lupus) (p < 0.0001), re-transplantation in primary APS (p = 0.0046) and shorter time since engraftment to SCr2 (p = 0.016). Primary APS was more often diagnosed post-transplant (p = 0.0005). Allograft biopsy revealed thrombotic microangiopathy (TMA) with acute rejection (AR) or isolated AR vs AR or chronic rejection in controls but did not reach significance (p = 0.054). Renal allograft function was inferior in the study group but did not reach significance: mean SCr2 (mg/dL) was 2.18 ± 1.41 and 1.5 ± 0.68 in controls, respectively, p = 0.27; mean GFR2 (ml/min/1.73m2) was 39.9 ± 20.83 and 51.23 ± 19.03, respectively, p = 0.102. Renal allograft duration was inferior in patients with APS and was (in years) 11.22 ± 1.44 vs. 14.36 ± 0.42, respectively, p = 0.037, in patients with primary APS (p = 0.021), in patients with APS diagnosed post-transplant (p = 0.012) but not in lupus-related APS (p = ns). Fifteen year renal allograft survival was inferior in APS vs. controls (73,86% vs. 90.48%, respectively, p = 0.049). Conclusions: Recipients with APS are at higher risk for allograft loss due to immune and non-immune causes. Renal allograft survival was inferior in recipients with APS and renal function remains impaired but stable.

Antiviral prophylaxis, male sex, and killer immunoglobulin-like receptor KIR2DL3 as markers for stratifying the risk of BK polyomavirus-associated nephropathy in kidney transplant recipients.

INTRODUCTION: The risk of polyomavirus­associated nephropathy (PyVAN) currently ranges from 1% to 10%, and the risk of graft loss is 10% to 50% within 2 years post­diagnosis. There is currently no specific antiviral therapy against BK polyomavirus (BKPyV), and no therapeutic approach has been proven superior. Natural killer cells play a key role in the defense against viral infections. OBJECTIVES: A retrospective, single­center cohort study was performed to investigate the association between the kidney transplant recipients' killer­cell immunoglobulin­like receptor (KIR) genotype and PyVAN. We also evaluated other possible risk factors for the occurrence of PyVAN in a population of kidney transplant recipients. PATIENTS AND METHODS: DNA samples from 134 kidney transplant recipients were identified for the presence or absence of variable KIR genes and their HLA ligands using polymerase chain reaction with sequence­specific primers. RESULTS: The analysis revealed that the presence of the inhibitory KIR2DL3 (P = 0.03) was a risk factor for posttransplant PyVAN. We also found that the presence of acute rejection before PyVAN (P = 0.02), male sex (P = 0.04), and the lack of antiviral prophylaxis (P = 0.01) were additional risk factors for posttransplant PyVAN. CONCLUSIONS: Our findings confirm that the KIR/HLA genotype plays a significant role in the development of PyVAN and suggest the contribution of both environmental and genetic factors to the incidence of BKPyV infection after kidney transplantation.

Immunity after COVID-19 Recovery and Vaccination: Similarities and Differences.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with a robust immune response. The development of systemic inflammation leads to a hyperinflammatory state due to cytokine release syndrome during severe COVID-19. The emergence of many new SARS-CoV-2 variants across the world deteriorates the protective antiviral immunity induced after infection or vaccination. The innate immune response to SARS-CoV-2 is crucial for determining the fate of COVID-19 symptomatology. T cell-mediated immunity is the main factor of the antiviral immune response; moreover, SARS-CoV-2 infection initiates a rapid B-cell response. In this paper, we present the current state of knowledge on immunity after COVID-19 infection and vaccination. We discuss the mechanisms of immune response to various types of vaccines (nucleoside-modified, adenovirus-vectored, inactivated virus vaccines and recombinant protein adjuvanted formulations). This includes specific aspects of vaccination in selected patient populations with altered immune activity (the elderly, children, pregnant women, solid organ transplant recipients, patients with systemic rheumatic diseases or malignancies). We also present diagnostic and research tools available to study the anti-SARS-CoV-2 cellular and humoral immune responses.

Noninvasive Diagnostic Methods for the Assessment of Hepatic Fibrosis in Liver Transplant Recipients.

BACKGROUND: Hepatic fibrosis in liver transplant recipients is the main predictive factor for graft function. Diagnostic methods for hepatic fibrosis staging should be available, reproducible, and noninvasive, if possible. We aimed to compare diagnostic methods for the assessment of hepatic fibrosis in transplant recipients: liver biopsy as a reference method, dynamic elastography, and direct and indirect blood markers (the ELF test [Enhanced Liver Fibrosis] test and the FibroTest). We sought to set a cutoff value for each method in order to assess significant liver fibrosis (F ≥2). METHODS: The study involved 62 patients after liver transplantation. Fibrosis was assessed in biopsy specimens using the METAVIR Score System (F0-F4). To identify clinically significant cutoff values of hepatic fibrosis (F ≥2, F ≥3, F = 4) for each method compared, a receiver-operating characteristic (ROC) curve analysis was used. RESULTS: Area under ROC for the prediction of significant fibrosis (F ≥2), advanced fibrosis (F ≥3), and cirrhosis (F = 4) for the study group was 0.5938, 0.8952, and 0.9583 for dynamic elastography; 0.7295, 0.7072, and 0.8409 for the ELF test; and 0.4863, 0.8049, and 0.8723 for the FibroTest. The cutoff value for F ≥2 for dynamic elastography was 4.65 kPa; for the ELF test, 9.27; and for the FibroTest, 0.72. CONCLUSIONS: The sensitivity and specificity of the tests studied, as compared with biopsy results, increase with increasing severity of hepatic fibrosis. The noninvasive diagnostic methods are of limited value in the diagnosis of early fibrosis stages. In the diagnostic assessment of hepatic fibrosis in its advanced stages, dynamic elastography can be used in conjunction with ELF test as a noninvasive alternative to liver biopsy.

Kidney Transplantation in a Patient With Tuberous Sclerosis Complex: A Case Report.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disease caused by mutations of either of 2 genes, TSC1 and TSC2. Renal manifestations include angiomyolipomas (AMLs), multiple cysts, and renal cell carcinoma. AMLs increase bleeding tendency and the risk of renal insufficiency which end-stage develops in 1% of affected patients. CASE REPORT: A 38-year-old woman suffering from TSC since early childhood has developed multiple complications associated with this disease. The patient was diagnosed with brain tumor-giant cell astrocytoma-which was removed in 1992. In 2006, right nephrectomy was performed due to the unsuccessful right renal artery embolization after the massive hemorrhage into the AML. Moreover, the right idiopathic pneumothorax occurred twice. Therefore, the video-assisted thoracoscopic surgery and pleurodesis were conducted (2006, 2013). The patient is intellectually disabled and unable to make decisions on her own. Her legal guardians (parents) make all decisions associated with her treatment. Diagnostic and therapeutic procedures demanding cooperation were conducted under anesthesia. Because of end-stage renal failure, the patient required the renal replacement therapy (RRT). Preemptive kidney transplantation (KTx) was the best solution for this patient. Procedures such as hemodialysis and peritoneal dialysis were infeasible to perform due to the intellectual disability that inhibits essential cooperation. During KTx qualification tests, the expanding AML with risk of hemorrhage was noticed. The patient was qualified for simultaneous left nephrectomy and KTx from the living donor (her father). The surgery was performed on the 2nd of June 2020. The patient is looked after by her parents, stays in good general condition. The patient's creatinine level is maintained at 0.6 to 0.8 mg/dL. CONCLUSION: Patients with significant intellectual disability that prevents maintaining conscious cooperation who require RRT must have individually adjusted therapy. In the case of the presented patient, it was decided to perform the preemptive kidney transplantation from her determined father.

Multidirectional facets of obesity management in the metabolic syndrome population after liver transplantation.

The obesity pandemic has resulted in an increasing demand for liver transplantation and has significantly altered the profile of liver transplant candidates in addition to affecting posttransplantation outcomes. In this review, we discuss a broad range of clinical approaches that warrant attention to provide comprehensive and patient-centred medical care to liver transplant recipients, and to be prepared to confront the rapidly changing clinical challenges and ensuing dilemmas. Adipose tissue is a complex and metabolically active organ. Visceral fat deposition is a key predictor of overall obesity-related morbidity and mortality. Limited pharmacological options are available for the treatment of obesity in the liver transplant population. Bariatric surgery may be an alternative in eligible patients. The rapidly increasing prevalence of nonalcoholic fatty liver disease (NAFLD) is a global concern; NAFLD affects both pre- and posttransplantation outcomes. Numerous studies have investigated pharmacological and nonpharmacological management of NAFLD and some of these have shown promising results. Liver transplant recipients are constantly exposed to numerous factors that result in intestinal microbiota alterations, which were linked to the development of obesity, diabetes type 2, metabolic syndrome (MS), NAFLD, and hepatocellular cancer. Microbiota modifications with probiotics and prebiotics bring gratifying results in the management of metabolic complications. Fecal microbiota transplantation (FMT) is successfully performed in many medical indications. However, the safety and efficacy profiles of FMT in immunocompromised patients remain unclear. Obesity together with immunosuppressive treatment, may affect the pharmacokinetic and/or pharmacodynamic properties of coadministered medications. Individualized immunosuppressive regimens are recommended following liver transplantation to address possible metabolic concerns. Effective and comprehensive management of metabolic complications is shown to yield multiple beneficial results in the liver transplant population and may bring gratifying results in improving long-term survival rates.

The molecular phenotypes of injury, steatohepatitis, and fibrosis in liver transplant biopsies in the INTERLIVER study.

To extend previous molecular analyses of rejection in liver transplant biopsies in the INTERLIVER study (ClinicalTrials.gov #NCT03193151), the present study aimed to define the gene expression selective for parenchymal injury, fibrosis, and steatohepatitis. We analyzed genome-wide microarray measurements from 337 liver transplant biopsies from 13 centers. We examined expression of genes previously annotated as increased in injury and fibrosis using principal component analysis (PCA). PC1 reflected parenchymal injury and related inflammation in the early posttransplant period, slowly regressing over many months. PC2 separated early injury from late fibrosis. Positive PC3 identified a distinct mildly inflamed state correlating with histologic steatohepatitis. Injury PCs correlated with liver function and histologic abnormalities. A classifier trained on histologic steatohepatitis predicted histologic steatohepatitis with cross-validated AUC = 0.83, and was associated with pathways reflecting metabolic abnormalities distinct from fibrosis. PC2 predicted histologic fibrosis (AUC = 0.80), as did a molecular fibrosis classifier (AUC = 0.74). The fibrosis classifier correlated with matrix remodeling pathways with minimal overlap with those selective for steatohepatitis, although some biopsies had both. Genome-wide assessment of liver transplant biopsies can not only detect molecular changes induced by rejection but also those correlating with parenchymal injury, steatohepatitis, and fibrosis, offering potential insights into disease mechanisms for primary diseases.

Assessment of the Banff Working Group classification of definitive BK polyomavirus nephropathy.

Polyomavirus associated nephropathy (PyVAN) continues to be a burden in renal transplantation leading to allograft insufficiency or graft failure. A presumptive diagnosis of PyVAN is made based on the presence of BK polyomavirus in patients' plasma; however, kidney biopsy remains the gold standard to establish a definitive diagnosis. The Banff Working Group on PyVAN proposed a novel classification of definitive PyVAN based on polyomavirus replication/load level and the extent of interstitial fibrosis. The aim of our study was to test the newly defined classes of PyVAN using independent cohorts of 124 kidney transplant patients with PyVAN with respect to the initial presentation and outcome, and to compare our analysis to that previously reported. Detailed analysis of our cohort revealed that the proposed classification of PyVAN did not stratify or identify patients at increased risk of allograft failure. Specifically, while class 3 was associated with the worst prognosis, there was no significant difference between the outcomes in classes 1 and 2. We also found that the timing post-transplantation and inflammation in areas of interstitial fibrosis and tubular atrophy might be additional factors contributing to an unfavorable allograft outcome in patients with PyVAN.

Treatment of recurrent urinary tract infections in a 60-year-old kidney transplant recipient. The use of phage therapy.

We would like to demonstrate the difficulty of treatment in a patient after kidney transplantation (KTX) who developed chronic urinary tract infection (UTI) with a multi-drug resistant ESBL-producing Klebsiella pneumoniae. The patient underwent several treatment interventions including supportive therapy with bacteriophages. This article presents a case of a 60-year-old patient after KTX repeatedly admitted to the hospital with recurrent UTIs caused by ESBL-producing Klebsiella pneumoniae showing variable susceptibility to carbapenems and full susceptibility to colistin only. KTX was performed due to renal insufficiency caused by polycystic kidney disease. The patient experienced 12 severe episodes of UTI due to K pneumoniae within 15 months since transplantation. In an attempt to curb the ongoing infections, phage therapy (PT) was applied on the experimental basis, coordinated by the Phage Therapy Unit of the Hirszfeld Institute in Wroclaw, Poland. Eventually, the patient fully recovered following nephrectomy of his own left kidney where cysts were the suspected reservoir of bacteria. The patient completed 29 days of PT. PT caused no reported side effects in the described case of the KTX recipient, although its role in controlling chronic UTI caused by K pneumoniae is unclear. More studies are needed in the population of kidney transplant recipients.

Formulas Estimating Glomerular Filtration Rate in the Evaluation of Living Kidney Donor Candidates: Comparison of Different Formulas With Scintigraphy-Measured Glomerular Filtration Rate.

INTRODUCTION: Estimation of kidney function is crucial in the evaluation of living kidney donor candidates. Despite the multitude of glomerular filtration rate (GFR) formulas, no equation is universal, and none were validated in the population of kidney donors. Novel biomarkers, including beta trace protein (BTP) and cystatin C, are studied to help estimate GFR and improve the safe qualification of living kidney donors. AIM: This study compares the accuracy of different formulas that estimate GFR with reference scintigraphy-measured GFR in the population of living kidney donor candidates. MATERIAL AND METHODS: This study enrolled 30 healthy living kidney donor candidates. GFR was measured using the following 11 different formulas. For reference, GFR was assessed using 99m-Technetium-diethylenetriaminepentaacetic acid. RESULTS: The accuracy of estimation was generally low in all formulas. The strongest correlation between measured GFR (mGFR) and estimated GFR (eGFR) was achieved by the Nankivell formula (R = 0.47, P = .009); however, in the group of patients with a body mass index of >25 kg/m2, only the equations based on BTP had a statistically significant correlation with mGFR: White (R = 0.59; P = .016) and Poge (R = 0.53; P = .035). Bland-Altman plots revealed wide limits of agreement between eGFRs and mGFR in all groups of patients. CONCLUSION: In living kidney donor candidates, GFR estimation formulas should be chosen individually. White formula, which is based on BTP, may be a promising tool in estimating GFR in overweight potential living kidney donor candidates. More than 1 formula and personalized choice of GFR estimation method regarding the given patient should be performed in qualification of kidney donors.

The switch from proteasome to immunoproteasome is increased in circulating cells of patients with fast progressive immunoglobulin A nephropathy and associated with defective CD46 expression.

The proteasome to immunoproteasome (iPS) switch consists of ß1, ß2 and ß5 subunit replacement by low molecular weight protein 2 (LMP2), LMP7 and multicatalytic endopeptidase-like complex-1 (MECL1) subunits, resulting in a more efficient peptide preparation for major histocompatibility complex 1 (MHC-I) presentation. It is activated by toll-like receptor (TLR) agonists and interferons and may also be influenced by genetic variation. In a previous study we found an iPS upregulation in peripheral cells of patients with immunoglobulin A nephropathy (IgAN). We aimed to investigate in 157 IgAN patients enrolled through the multinational Validation Study of the Oxford Classification of IgAN (VALIGA) study the relationships between iPS switch and estimated glomerular filtration rate (eGFR) modifications from renal biopsy to sampling. Patients had a previous long follow-up (6.4 years in median) that allowed an accurate calculation of their slope of renal function decline. We also evaluated the effects of the PSMB8/PSMB9 locus (rs9357155) associated with IgAN in genome-wide association studies and the expression of messenger RNAs (mRNAs) encoding for TLRs and CD46, a C3 convertase inhibitor, acting also on T-regulatory cell promotion, found to have reduced expression in progressive IgAN. We detected an upregulation of LMP7/ß5 and LMP2/ß1 switches. We observed no genetic effect of rs9357155. TLR4 and TLR2 mRNAs were found to be significantly associated with iPS switches, particularly TLR4 and LMP7/ß5 (P < 0.0001). The LMP7/ß5 switch was significantly associated with the rate of eGFR loss (P = 0.026), but not with eGFR at biopsy. Fast progressors (defined as the loss of eGFR >75th centile, i.e. -1.91 mL/min/1.73 m2/year) were characterized by significantly elevated LMP7/ß5 mRNA (P = 0.04) and low CD46 mRNA expression (P < 0.01). A multivariate logistic regression model, categorizing patients by different levels of kidney disease progression, showed a high prediction value for the combination of high LMP7/ß5 and low CD46 expression.